Preparation of 3,4-dihydroanthracen-1(2H)-ones. A synthetic approach to islandicin and digitopurpone via difluoro[anthracen-1(2H)-onato-O1,O9]boron chelates

Abstract

Three 9,10-dihydroxyanthracen-1(2H)-one derivatives (2a–c) have been obtained by the catalytic hydrogenation of quinizarin, 1-hydroxy-5-methoxyanthraquinone, and 1-hydroxy-8-methoxyanthraquinone, respectively; in the last two reactions, monohydroxyanthracen-1(2H)-ones (4a) and (4b) are formed as by-products. The anthracenone derivatives (2a–c) were O-methylated by methyl toluene-p-sulphonate and the selective demethylation of the dimethoxy derivative (2d) to the monomethoxy derivative (2e) was effected by AlCl₃. The silyl enolate (5) was unreactive toward C-methylation but the lithium enolate of the anthracenone (2d) reacted with methyl iodide to give a mixture of C-mono (2f) and C-di (6a) alkylated derivatives; in contrast, the boron enolate of (2d) reacted with methyl iodide to give exclusively the C-monomethylated derivative (2f) and this procedure was extended to the synthesis of 5-methoxy (2g) and 8-methoxy (2h) analogues of (2f). Whereas the dimethoxyanthracenone derivative (2d) is brominated (Br₂–CHCl₃, 0 °C) in separate reactions to give monobromo (2i) and dibromo (6b) derivatives, the difluoroboron chelate (9a)[from (2d) and BF₃–Et₂O] was converted by photochemical bromination into a product (9g) of benzylic substitution; the analogue (9h) was similarly obtained from the difluoroboron chelate (9b). The boron derivatives (9g) and (9h) were transformed by methanol into hydroxydimethoxyanthracenone derivatives (2l) and (2m), and (9g) was also converted by wet alumina into the dihydroxymethoxyanthracenone (2n). The hydroxydimethoxyanthracenones (2l) and (2m) were transformed by 2,3-dichloro-5,6-dicyanobenzoquinone [for (2l)] and selenium dioxide [for (2n)] into 1-hydroxy-4-methoxyanthraquinone and 1-hydroxy-4-methoxy-2-methylanthraquinone, respectively.